title: Circulating miRNAs reflect early myocardial injury and recovery after heart transplantation.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are short, single-stranded and non-coding RNAs, freely circulating in human plasma and correlating with vary pathologies. In this study, we monitored early myocardial injury and recovery after heart transplantation by detecting levels of circulating muscle-specific miR-133a, miR-133b and miR-208a.
  
  
  METHODS
  7 consecutive patients underwent heart transplantation in Fuwai hospital and 14 healthy controls were included in our study. Peripheral vein blood was drawn from patients on the day just after transplantation (day 0), the 1st, 2nd, 3rd, 7th and 14th day after transplantation respectively. Serum from peripheral blood was obtained for cardiac troponin I (cTnI) measurement. Plasma was centrifuged from peripheral blood for measuring miR-133a, miR-133b and miR-208a by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The plasma concentration of miRNAs were calculated by absolute quantification method. The sensitivity and specificity of circulating miRNAs were revealed by receiver operating characteristic curve (ROC) analysis. Correlations between miRNAs and cTnI / perioperative parameters were analyzed.
  
  
  RESULTS
  Similar to cTnI, miR-133a, miR-133b and miR-208a all showed dynamic changes from high to low levels early after operation. The Sensitivity and specificity of miRNAs were: miR-133a (85.7%,100%), miR-208a (100%,100%), and miR-133b (90%,100%). Correlations between miRNAs and cTnI were statistically significant (p < 0.05), especially for miR-133b (R2 = 0.813, p < 0.001). MiR-133b from Day 0-Day 2 (r > 0.98, p < 0.01), and cTnI from Day 1- Day 3 (r > 0.86, p < 0.05) had strong correlations with bypass time, particularly parallel bypass time. Obviously, miR-133b had a better correlation than cTnI. Circulating miR-133b correlated well with parameters of heart function such as central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO) and inotrope support, while cTnI only correlated with 3 of the 4 parameters mentioned above. MiR-133b also had strong correlations with ventilation time (r > 0.99, p < 0.001) and length of ICU stay (r > 0.92, p < 0.05), both of which reflected the recovery after operation. The correlation coefficients of miR-133b were also higher than that of cTnI.
  
  
  CONCLUSIONS
  The dynamic change in circulating muscle-specific miRNAs, especially miR-133b can reflect early myocardial injury after heart transplantation. And miR-133b may have advantages over cTnI in forecasting graft dysfunction and recovery of patients after operation.
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People's Republic of China.
authors.forename: Enshi
authors.initials: E
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Nie
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.forename: Zhongkai
authors.initials: Z
authors.lastname: Liao
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Shengshou
authors.initials: S
authors.lastname: Hu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zheng
mesh_terms: D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011183:Postoperative Complications / Q000097:blood*; D012372:ROC Curve; D015427:Reperfusion Injury / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D019210:Troponin I / Q000097:blood
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D019210:Troponin I